Estrogen tied to liver damage in women drinkers

Researchers at Juntendo University have identified the role of a female hormone that they say leads to alcohol-induced liver damage among women.

The research team, led by gastroenterology professor Nobuhiro Sato, found that alcohol intake increases levels of the female hormone estrogen, a substance that causes liver inflammation.

Sato, who experimented on rats, said he hopes to apply the discovery to the treatment and prevention of liver diseases.

Women are generally held to be more sensitive than men to the effects of alcohol — and more vulnerable to liver ailments, such as alcohol-induced hepatitis and cirrhosis — due to their relatively small body frames and smaller livers, as well as hormonal effects.

The experiments conducted by Sato’s team focused on the mechanism whereby the liver decomposes endotoxin, a toxic substance produced by intestinal cultures after it is activated by alcohol.

Sato’s team found that while Kupffer cells in the liver decompose endotoxin, the same cells also produce a substance called cytokine (TNF-alpha), which destroys surrounding cells in the liver and causes inflammation.

To identify the role of estrogen in this process, Sato’s team gave alcohol to two groups of female rats. One group was injected with estrogen and the other was not.

In the livers of the rats injected with estrogen, the endotoxin receptors located on the surface of Kupffer cells increased threefold. This in turn led to a threefold increase in the output of cytokines, causing serious liver damage.

Sato believes that if doctors can identify a specific gene related to the production of cytokines, they may, one day, be able to suppress alcohol-induced liver damage.

But gastroenterologist Satoshi Takagi, the director of Shinmachi Clinic’s health management center, cast doubt on the findings.

Takagi said that epidemiologic research has already established that women are more susceptible to liver ailments from a small amount of alcohol than males, but the ailments are of a short duration.

He said the effect of estrogen alone does not fully explain the problem, pointing out that the percentage of women with liver diseases is smaller than among men.

“The female hormone’s impact could be one of many factors. The fact that women will become alcohol-dependent more quickly than men may explain the root of the problem,” Takagi said.